Ventricular hypertrophy is an important adaptive mechanism which accompanies systemic arterial hypertension. However, at some point in time, this compensatory process results in congestive heart failure. The major objectives of our research program, is to define the fundamental mechanical, biochemical and molecular biologic properties of pressure overload hypertrophy and hypertrophy regression in a unique model of gradual onset renal hypertension in the non-human primate (baboon). Parallel studies in a smaller mammal (guinea pig) are proposed to elucidate species differences, to facilitate development of analytic techniques, and to examine cardiac chamber mechanics of pressure overload hypertrophy in the isolated heart which is devoid of the influences of neurohumoral factors and ventricular vascular coupling. Using this approach, we propose to test the following specific hypotheses: 1) pressure overload hypertrophy is associated with unchanged systolic chamber elastance, load independent reduced velocities of ejection and filling and elevated passive chamber and muscle stiffness; 2) regression of pressure overload hypertrophy is characterized by normalization of velocities of ejection and filling and residually elevated cardiac muscle stiffness; 3) pressure overload hypertrophy is associated with diminished high-energy phosphate reserves in response to physiologic stress which is reversible upon hypertrophy regression; 4) reversibly reduced myosin ATPase activity underlies diminished velocities of shortening and relaxation during pressure overload hypertrophy and is caused by transcriptional and/or translational alterations in beta myosin heavy chains; 5) coordinate transcriptional and translational alteration of myosin light chains exert a modulatory role on myosin ATPase activity and mechanical behavior in pressure overload hypertrophy and regression; and 6) transcriptional alterations in collagen amount distribution and type largely determine intrinsic passive chamber properties of hypertrophied and hypertrophy regressed myocardium.